A number of advanced cancers such as renal cell carcinoma and squamous cell carcinoma of the lung have proven particularly refractory to chemotherapy. It is therefore warranted to test new agents or new experimental modalities in these tumors. Animal studies suggest that the chemotherapeutic activity of certain alkylating agents can be augmented by the use of dimethylsulfoxide (DMSO). Patients with metastatic squamous cell carcinoma were therefore tested with DMSO and cyclophosphamide. Ten patients with squamous cell lung cancer have been started on DMSO plus cyclophosphamide. There have been no objective anti-tumor responses seen in three patients, but it is too early to determine overall activity of this combination. Pharmacokinetics have been initiated to determine if the DMSO changes the disposition of the cyclophosphamide. So far no differences have been noted where each patient serves as his/her own control.